title: Effects of atopy and grass pollen season on histamine H₄ receptor expression in human leukocytes.
abstract: BACKGROUND
  The histamine H4 receptor (H4R) is a novel therapeutic target to treat allergic inflammation.
  
  
  OBJECTIVE
  To profile messenger RNA (mRNA) expression of H₄R isoforms in human cells and evaluate the effects of atopy and grass pollen season on H₄R expression in peripheral blood leukocytes ex vivo.
  
  
  METHODS
  H₄R isoform expression was assayed by quantitative polymerase chain reaction in human airway and peripheral RNA. During low and high grass pollen seasons, leukocytes were isolated from venous blood and fractionated into peripheral blood mononuclear cells and polymorphonuclear cells (PMN). H₄R expression was determined and related to atopy, defined by a level of specific IgE to Timothy grass pollen of ≥0.35 kU(A)/L (n = 7 atopic patients and 9 controls).
  
  
  RESULTS
  Expression of total and full length H₄R was at the limit of detection but predominant in peripheral blood leukocytes, where truncated H₄R was expressed exclusively (≤300-fold less). Suggestive evidence for total H₄R in airway cells and brain indicated an expression ≤260-fold lower than in peripheral blood mononuclear cells. Total H₄R mRNA expression was unaffected by atopy or grass pollen season, but truncated H₄R was significantly reduced during high grass pollen season in total leukocytes, independently of atopy (P < .01).
  
  
  CONCLUSIONS
  H₄R mRNA is predominantly expressed in peripheral blood leukocytes, and total H₄R expression levels are unrelated to atopy or grass pollen season. Atopy-independent seasonal variation in truncated H₄R expression might affect putative negative regulation of full length H4R during high grass pollen season. If verified, this should be considered during the design of drugs targeting H₄R to treat allergic inflammation, particularly for seasonal allergic rhinitis.
authors.affiliation: Division of Therapeutics and Molecular Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom. Emily.Hodge@nottingham.ac.uk
authors.forename: Emily
authors.initials: E
authors.lastname: Hodge
authors.forename: William Y C
authors.initials: WY
authors.lastname: Chang
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Selby
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
authors.forename: Ian
authors.initials: I
authors.lastname: Sayers
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011058:Pollen / Q000276:immunology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011968:Receptors, Histamine / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000378:metabolism; D011795:Surveys and Questionnaires
chemical_list: D000485:Allergens; C418607:HRH4 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D007073:Immunoglobulin E